Cocaine dependence is a serious public health problem in the general population and among methadone maintenance patients in treatment for opioid dependence. Recent epidemiologic studies also indicate that intravenous use of cocaine may represent an additional risk factor for the acquisition of the human immunodeficiency virus among patients with opioid dependence. The discovery of endogenous brain reward circuitry and the characterization of the self-administration of cocaine in animal models indicate that dopamine agonists may be useful agents for the attenuation of cocaine craving and use in humans. Pilot studies using the indirect dopamine agonist, amantadine, support this hypothesis. A double-blind, placebo- controlled trial of amantadine at two dosages is now proposed to be tested in methadone-maintained patients who also meet DSM-III-R criteria for cocaine dependence. Ninety subjects, thirty per each experimental group, will be required for completion of the protocol. The design will employ a random assignment, between-groups, eight-week comparative trial of two doses of amantadine vs. placebo. In contrast to a previous submission, the issue of relapse after amantadine treatment has been relegated to a second- level aim. This issue will not be examined in the formal protocol, but will be investigated using data that arise naturally in the methadone maintenance program. The major outcome variables will be level of cocaine use and craving in the course of amantadine treatment. The major predictor variables will be amantadine dosage group as well as demographic and psychological variables measured at enrollment into the protocol. The study is also designed to extract information about the relationship of cocaine craving and cocaine use, and the role of environmental and internal cues which may control craving and drug-seeking behavior. Amantadine is one of a growing panel of direct and indirect dopamine agonists which hold promise as potential treatments for cocaine dependence. The apparent efficacy of amantadine in pilot studies and its relatively benign profile of side effects are factors which support the indications for blind, placebo-controlled clinical trials at this time. The setting of this study among methadone-maintained patients will minimize problems with attrition since methadone maintenance is associated with good retention in treatment. The study will determine whether this population of high-risk cocaine- dependent patients can be treated effectively with amantadine over an eight week period.